1. Field of the Invention
The present invention relates to a DNA vaccine and its preparation, which employs DNA recombination technique to co-incorporate at least one fragment of tumor-associated gene and at least one fragment of cytokine gene into a vector, thereby producing a DNA vaccine containing at least one fragment of tumor-associated gene and at least one fragment of cytokine gene simultaneously.
2. Description of Related Art
The immunotherapy for cancer is drawing more and more attention in recent years. In particular, due to the development of molecular biology and the progress of biotechnology, there has been a significant breakthrough in DNA vaccine development. Current available cancer vaccines include at least DNA vaccine, dendritic cell vaccine and gene-modified tumor vaccine etc. Unlike a typical vaccine used for disease prevention, cancer vaccine aims at cancer treatment. More specifically, the purpose of cancer vaccine is to boost self-immunity for tumor cells and enable the immune system to recognize as well as kill tumor cells. DNA vaccine transforms genes encoding specific tumor-associated antigens (e.g. oncogene such as neu, met or ras) into host cells where said tumor-associated antigens are expressed through transcription and translation to induce the immune response of the host against said tumor-associated antigens and to inhibit or suppress the growth of tumor cells.
Take oncogene neu (also known as Her-2 or c-erbB-2) as an example, previous studies indicated that neu gene was over-expressed in the tumor tissues of some patients with lung cancer, breast cancer, ovarian cancer or bladder cancer. Oncogene neu encodes a transmembrane glycoprotein, which is a growth factor receptor receiving signals to expedite cell growth and division. Since the overexpression of neu gene and propagation of tumor cells are positively related, neu gene may be considered as a tumor-associated antigen. In addition, the overexpression of neu gene is also related to drug resistance in medication; patients with such symptom usually have poor prognosis.
Because of its overexpression in certain types of cancer, neu gene can be used to design cancer vaccines targeting the gene itself, for instance, a DNA vaccine carrying neu gene. The combination of neu DNA vaccine and cytokine-specific tumor vaccine, such as Interleukin-2 (IL-2), Interleukin-4 (IL-4), and GM-CSF (granulocyte macrophage colony-stimulating factor) has shown its capability to inhibit the growth of tumor cells in mice. However, the preparation of such tumor vaccine requires prolonged in vitro culture and an extra tumor cells screening process. While culturing, mutation is prone to occur and results in the loss of surface antigen; while screening, the heterogeneity of the tumor cells might decrease and reduce the protection of tumor vaccine. Moreover, it is costly to prepare this type of vaccine, and its clinical application is still not popular so far.